tbuckley/cabot-search huggingface dataset:
Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury
Authors: Bo Cao, Rui-Yang Zhao, Hang-Hang Li, Xing-Ming Xu, Hao Cui, Huan Deng, Lin Chen, Bo Wei
Journal: Military Medical Research (2022)

Traumatic colon injury (TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However, there is a lack of basic research in this field. This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield.A total of 669 Sprague-Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase, D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis, the relative abundances of specific bacterial genera were detected using quantitative real-time PCR.As a type of lethal injury, TCI induced acute disruption of intestinal homeostasis, characterized by inflammatory responses, intestinal barrier hyperpermeability and microbiota dysbiosis (P < 0.05). Significant alterations in bacterial metabolic patterns were detected with decreases in many metabolites. After a series of screenings, we found that oral administration of asparagine (Asn) and 3-indolepropionic acid (IPA) effectively prolonged posttraumatic survival time [Asn plus IPA vs. Vehicle: hazard ratio (HR) = 0.105, 95% CI 0.031-0.356, P = 0.0003] and restored intestinal homeostasis in TCI rats (P < 0.05). Mechanistically, this combinational strategy protected the rats against TCI through synergistic activation of Akt signaling in the intestinal epithelium (P < 0.05).Abrupt dysregulation of intestinal homeostasis plays a critical role in the progression toward TCI-induced death. Oral administration of Asn plus IPA may serve as an effective regimen to restore intestinal functions and prolong the posttraumatic survival time.
Sex and Drug Overdose Mortality Trends, 1999-2020
Authors: Rebecca Arden Harris
Journal: JAMA Psychiatry (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Biomarker‐driven prognostic models in chronic heart failure with preserved ejection fraction: the <scp>EMPEROR</scp>–Preserved trial
Authors: Stuart J. Pocock, João Pedro Ferreira, Milton Packer, Faiez Zannad, Gerasimos Filippatos, Toru Kondo, John J.V. McMurray, Scott D. Solomon, James L. Januzzi, Tomoko Iwata, Afshin Salsali, Javed Butler, Stefan D. Anker
Journal: European Journal of Heart Failure (2022)

ABSTRACT Aims Biomarker‐driven prognostic models incorporating N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity cardiac troponin T (hs‐cTnT) in heart failure (HF) with preserved ejection fraction (HFpEF) are lacking. We aimed to generate a biomarker‐driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR‐Preserved. Methods and results Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death, (ii) all‐cause death, (iii) cardiovascular death, and (iv) HF hospitalization. PARAGON‐HF was used as a validation cohort. NT‐proBNP and hs‐cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last hospitalization, New York Heart Association (NYHA) class III or IV, history of chronic obstructive pulmonary disease (COPD), insulin‐treated diabetes, low haemoglobin, and a longer time since HF diagnosis were key predictors (eight variables, all p &lt; 0.001). The consequent primary outcome risk score discriminated well ( c ‐statistic = 0.75) with patients in the top 10th of risk having an event rate &gt;22× higher than those in the bottom 10th. A model for HF hospitalization alone had even better discrimination ( c = 0.79). Empagliflozin reduced the risk of cardiovascular death or hospitalization for HF in patients across all risk levels. NT‐proBNP and hs‐cTnT were also the dominant predictors of all‐cause and cardiovascular mortality followed by history of COPD, low albumin, older age, left ventricular ejection fraction ≥50%, NYHA class III or IV and insulin‐treated diabetes (eight variables, all p &lt; 0.001). The mortality risk model had similar discrimination for all‐cause and cardiovascular mortality ( c ‐statistic = 0.72 for both). External validation provided c ‐statistics of 0.71, 0.71, 0.72, and 0.72 for the primary outcome, HF hospitalization alone, all‐cause death, and cardiovascular death, respectively. Conclusions The combination of NT‐proBNP and hs‐cTnT along with a few readily available clinical variables provides effective risk discrimination both for morbidity and mortality in patients with HFpEF. A predictive tool‐kit facilitates the ready implementation of these risk models in routine clinical practice.
Time to Revisit Using 10-Year Risk to Guide Statin Therapy
Authors: Ann Marie Navar, Gregg C. Fonarow, Michael J. Pencina
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Pulse oximetry and the pandemic
Authors: Paul Silverston, Marco Ferrari, Valentina Quaresima
Journal: BMJ (2022)

<h3>Objectives</h3> Quality concerns in STI service delivery and missed opportunities for integration with HIV testing and prevention services in South Africa have been well documented. This national evaluation aimed to evaluate current utilisation and adherence to national STI guidelines, including partner notification and integration with HIV services, for diagnosis and management of STIs. <h3>Methods</h3> Facility surveys assessed infrastructure and resource availability, and standardised patient (SP) assessments evaluated quality of STI care in 50 public clinics in nine provinces in South Africa. The primary outcome was the proportion of SPs receiving essential STI care, defined as: offered an HIV test, condoms, partner notification counselling and correct syndromic treatment. Weighted proportions were generated, and SP findings were compared by gender using χ<sup>2</sup> tests with Rao-Scott correction. <h3>Results</h3> More than 80% of facilities reported medications in stock, with the exceptions of oral cefixime (48.3%), oral erythromycin (75.1%) and paediatric syrups. Among 195 SP encounters, 18.7% (95% CI 10.7% to 30.5%) received all hypothesised essential STI services: offered HIV test (67.1%), offered condoms (31.4%), partner notification counselling (70.2%) and recommended syndromic treatment (60.7%). Men were more likely than women to be offered all services (25.1% vs 12.3%, p=0.023), recommended treatment (70.7% vs 50.9%, p=0.013) and partner notification counselling (79.9% vs 60.6%, p=0.020). Only 6.3% of providers discussed male circumcision with male SPs, and 26.3% discussed family planning with female SPs. <h3>Conclusions</h3> This evaluation of STI services across South Africa found gaps in the availability of medications, adherence to STI guidelines, condom provision and prevention messaging. Limited integration with HIV services for this high-risk population was a missed opportunity. Quality of STI care should continue to be monitored, and interventions to improve quality should be prioritised as part of national strategic HIV and primary healthcare agendas.
Avidity in antibody effector functions and biotherapeutic drug design
Authors: Simone C. Oostindie, Greg A. Lazar, Janine Schuurman, Paul W. H. I. Parren
Journal: Nature Reviews Drug Discovery (2022)

Antibodies are the cardinal effector molecules of the immune system and are being leveraged with enormous success as biotherapeutic drugs. A key part of the adaptive immune response is the production of an epitope-diverse, polyclonal antibody mixture that is capable of neutralizing invading pathogens or disease-causing molecules through binding interference and by mediating humoral and cellular effector functions. Avidity — the accumulated binding strength derived from the affinities of multiple individual non-covalent interactions — is fundamental to virtually all aspects of antibody biology, including antibody–antigen binding, clonal selection and effector functions. The manipulation of antibody avidity has since emerged as an important design principle for enhancing or engineering novel properties in antibody biotherapeutics. In this Review, we describe the multiple levels of avidity interactions that trigger the overall efficacy and control of functional responses in both natural antibody biology and their therapeutic applications. Within this framework, we comprehensively review therapeutic antibody mechanisms of action, with particular emphasis on engineered optimizations and platforms. Overall, we describe how affinity and avidity tuning of engineered antibody formats are enabling a new wave of differentiated antibody drugs with tailored properties and novel functions, promising improved treatment options for a wide variety of diseases. Antibody function is dependent on avidity — the accumulated strength of multiple affinity interactions between the antibody, antigen, cell surface receptors and other antibodies. In this Review, Oostindie et al. discuss the role of avidity in eliciting antibody functional responses and review the current engineering strategies for manipulating avidity interactions in antibody-based therapies.
Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus
Authors: Ronald F van Vollenhoven, Kenneth C Kalunian, Thomas Dörner, Bevra H Hahn, Yoshiya Tanaka, Robert M Gordon, Cathye Shu, Kaiyin Fei, Sheng Gao, Loqmane Seridi, Patrick Gallagher, Kim Hung Lo, Pamela Berry, Qing C Zuraw
Journal: Annals of the Rheumatic Diseases (2022)

Objective Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care. Methods Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24. Results At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event. Conclusions Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab. Trial registration number NCT03517722 .
Highlights From the <i>Circulation</i> Family of Journals
Journal: Circulation (2022)

A range of intriguing cardiovascular studies from the Circulation family of journals is highlighted this month.The association of new-onset atrial fibrillation with cardiovascular outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19) is described in Circulation: Arrhythmia and Electrophysiology.Rates of cardiovascular and cerebrovascular disease mortality among Asian subgroups are presented in Circulation: Cardiovascular Quality and Outcomes.Blood pressure and glycemic control are presented in patients with heart failure in Circulation: Heart Failure.Associations of atrial uptake on technetium-99m-pyrophosphate scans for transthyretin amyloid cardiomyopathy with incident atrial fibrillation and possibly earlier diagnosis of amyloid are presented in Circulation: Cardiovascular Imaging.The outcomes associated with larger burdens of residual thrombus after aspiration thrombectomy for ST-segment-elevation myocardial infarction are presented in Circulation: Cardiovascular Interventions.
Hospitalization Outcomes Among Patients With COVID-19 Undergoing Remote Monitoring
Authors: Bradley H. Crotty, Yilu Dong, Purushottam Laud, Ryan J. Hanson, Bradley Gershkowitz, Annie C. Penlesky, Neemit Shah, Michael Anderes, Erin Green, Karen Fickel, Siddhartha Singh, Melek M. Somai
Journal: JAMA Network Open (2022)

Health care systems have implemented remote patient monitoring (RPM) programs to manage patients with COVID-19 at home, but the associations between participation and outcomes or resource utilization are unclear.
Association Between Perceived Race and Operative Autonomy in General Surgery Residents
Authors: Luke Pumiglia, Kenneth L. Abbott, Roberta Ukavwe, Kaavya S. Puttagunta, Kankanit Thanapuasuwan, Katherine E. Neff, Gifty Kwakye
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Endothelial PHD2 deficiency induces nitrative stress<i>via</i>suppression of caveolin-1 in pulmonary hypertension
Authors: Bin Liu, Yi Peng, Dan Yi, Narsa Machireddy, Daoyin Dong, Karina Ramirez, Jingbo Dai, Rebecca Vanderpool, Maggie M. Zhu, Zhiyu Dai, You-Yang Zhao
Journal: European Respiratory Journal (2022)

Nitrative stress is a characteristic feature of the pathology of human pulmonary arterial hypertension. However, the role of nitrative stress in the pathogenesis of obliterative vascular remodelling and severe pulmonary arterial hypertension remains largely unclear.Our recently identified novel mouse model (Egln1Tie2Cre, Egln1 encoding prolyl hydroxylase 2 (PHD2)) has obliterative vascular remodelling and right heart failure, making it an excellent model to use in this study to examine the role of nitrative stress in obliterative vascular remodelling.Nitrative stress was markedly elevated whereas endothelial caveolin-1 (Cav1) expression was suppressed in the lungs of Egln1Tie2Cre mice. Treatment with a superoxide dismutase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride or endothelial Nos3 knockdown using endothelial cell-targeted nanoparticle delivery of CRISPR-Cas9/guide RNA plasmid DNA inhibited obliterative pulmonary vascular remodelling and attenuated severe pulmonary hypertension in Egln1Tie2Cre mice. Genetic restoration of Cav1 expression in Egln1Tie2Cre mice normalised nitrative stress, reduced pulmonary hypertension and improved right heart function.These data suggest that suppression of Cav1 expression secondary to PHD2 deficiency augments nitrative stress through endothelial nitric oxide synthase activation, which contributes to obliterative vascular remodelling and severe pulmonary hypertension. Thus, a reactive oxygen/nitrogen species scavenger might have therapeutic potential for the inhibition of obliterative vascular remodelling and severe pulmonary arterial hypertension.
The intestinal microbial metabolite nicotinamide n-oxide prevents herpes simplex encephalitis via activating mitophagy in microglia
Authors: Feng Li, Yiliang Wang, Xiaowei Song, Zhaoyang Wang, Jiaoyan Jia, Shurong Qing, Lianzhou Huang, Yuan Wang, Shuai Wang, Zhe Ren, Kai Zheng, Yifei Wang
Journal: Gut Microbes (2022)

Herpes simplex encephalitis (HSE), a complication of herpes simplex virus type I (HSV-1) infection causes neurological disorder or even death in immunocompromised adults and newborns. However, the intrinsic factors controlling the HSE outcome remain unclear. Here, we show that HSE mice exhibit gut microbiota dysbiosis and altered metabolite configuration and tryptophan-nicotinamide metabolism. HSV-1 neurotropic infection activated microglia, with changed immune properties and cell numbers, to stimulate antiviral immune response and contribute substantially to HSE. In addition, depletion of gut microbiota by oral antibiotics (ABX)-treatment triggered the hyper-activation of microglia, which in turn enhanced inflammatory immune response, and cytokine production, resulting in aggregated viral burden and HSE pathology. Furthermore, exogenous administration of nicotinamide n-oxide (NAMO), an oxidative product of nicotinamide derived from gut microbiota, to ABX-treated or untreated HSE mice significantly diminished microglia-mediated proinflammatory response and limited HSV-1 infection in CNS. Mechanistic study revealed that HSV-1 activates microglia by increasing mitochondrial damage via defective mitophagy, whereas microbial metabolite NAMO restores NAD+-dependent mitophagy to inhibit microglia activation and HSE progression. NAMO also prevented neuronal cell death triggered by HSV-1 infection or microglia-mediated microenvironmental toxicity. Finally, we show that NAMO is mainly generated by neomycin-sensitive bacteria, especially Lactobacillus_gasseri and Lactobacillus_reuteri. Together, these data demonstrate that gut microbial metabolites act as intrinsic restrictive factors against HSE progression via regulating mitophagy in microglia, implying further exploration of bacterial or nutritional approaches for treating neurotropic virus-related neurodegenerative diseases.
Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors
Authors: Liangliang Xu, Chang Zou, Shanshan Zhang, Timothy Shun Man Chu, Yan Zhang, Weiwei Chen, Caining Zhao, Li Yang, Zhiyuan Xu, Shaowei Dong, Hao Yu, Bo Li, Xinyuan Guan, Yuzhu Hou, Feng-Ming Kong
Journal: Journal of Hematology & Oncology (2022)

The development of combination immunotherapy based on the mediation of regulatory mechanisms of the tumor immune microenvironment (TIME) is promising. However, a deep understanding of tumor immunology must involve the systemic tumor immune environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial transcriptomics for the studies of STIE, TIME, and their interactions, which may reveal heterogeneity in immunotherapy responses as well as the dynamic changes essential for the treatment effect. We review the evidence from preclinical and clinical studies related to TIME, STIE, and their significance on overall survival, through different immunomodulatory pathways, such as metabolic and neuro-immunological pathways. We also evaluate the significance of the STIE, TIME, and their interactions as well as changes after local radiotherapy and systemic immunotherapy or combined immunotherapy. We focus our review on the evidence of lung cancer, hepatocellular carcinoma, and nasopharyngeal carcinoma, aiming to reshape STIE and TIME to enhance immunotherapy efficacy.
Memory-enhancing properties of sleep depend on the oscillatory amplitude of norepinephrine
Authors: Celia Kjaerby, Mie Andersen, Natalie Hauglund, Verena Untiet, Camilla Dall, Björn Sigurdsson, Fengfei Ding, Jiesi Feng, Yulong Li, Pia Weikop, Hajime Hirase, Maiken Nedergaard
Journal: Nature Neuroscience (2022)